Title:Molecular Aspects of Melatonin Treatment in Tinnitus: A Review
Volume: 20
Issue: 11
Author(s): Azam Hosseinzadeh, Seyed Kamran Kamrava, Brian C.J. Moore, Russel J. Reiter, Habib Ghaznavi, Mahboobeh Kamali and Saeed Mehrzadi*
Affiliation:
- Razi Drug Research Center, Iran University of Medical Sciences, Tehran,Iran
Keywords:
Tinnitus, melatonin, neural plasticity, oxidative stress, autophagy, apoptosis.
Abstract: Tinnitus is a hearing disorder characterized by the perception of sound without external
acoustic stimuli, which is caused by damage to the auditory system in response to excessive levels of
noise, ototoxic agents and aging. Neural plasticity, oxidative/nitrosative stress and apoptosis play important
roles in the pathogenesis of tinnitus. The expression of neural plasticity related to excessive
glutamatergic neurotransmission leads to generation of abnormal sound in one's ears or head. Furthermore,
hyperactivation and over-expression of NMDA receptors in response to excessive release of
glutamate contribute to the calcium overload in the primary auditory neurons and subsequent cytotoxicity.
Reactive oxygen/nitrogen species are endogenously produced by different type of cochlear cells
under pathological conditions, which cause direct damage to the intracellular components and apoptotic
cell death. Cochlear hair-cell death contributes to the progressive deafferentation of auditory neurons,
which consequently leads to the aberrant activity in several parts of the auditory pathway. Therefore,
targeting neural plasticity, oxidative/nitrosative stress, apoptosis and autophagy may ameliorate
tinnitus. Melatonin is an endogenously produced indoleamine synchronizing circadian and circannual
rhythms. Based on laboratory studies indicating the protective effect of melatonin against cochlear
damage induced by acoustic trauma and ototoxic agents, and also clinical studies reporting the ability
of melatonin to minimize the severity of tinnitus, melatonin is suggested to be a treatment option for
the patient with tinnitus. Herein, we describe the ameliorative effect of melatonin on tinnitus, focusing
on neural plasticity, oxidative/nitrosative stress, apoptotsis and autophagy.
